Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-Deoxy-D-ribose
Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-Deoxy-D-ribose
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DOI：
10.1006/bbrc.2002.6432
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发表时间：
2002-03-08
影响因子：
3.1
通讯作者：
Akiyama, S
中科院分区：
文献类型：
--
作者：
Ikeda, R;Furukawa, T;Akiyama, S
血小板源性内皮细胞生长因子/胸苷磷酸化酶 (PD-ECGF/TP) 是一种血管生成因子，可刺激内皮细胞的趋化性并赋予对缺氧诱导的细胞凋亡的抵抗力。 2-DeOXY-D-核糖是 TP 酶活性产生的胸苷降解产物，可部分阻止缺氧诱导的细胞凋亡。 2-DeOXy-D-ribose 抑制 caspase 介导的缺氧诱导的细胞凋亡途径的许多成分。它可抑制人白血病 HL-60 细胞系中缺氧诱导的 caspase 3 激活、线粒体细胞色素 c 释放、Bcl-2 和 Bcl-x(L) 下调、缺氧诱导因子 (HIF)-1α 上调以及线粒体跨膜电位丧失。这些发现提示了 2-deOXY-D-核糖赋予细胞凋亡抵抗力的分子机制。因此，2-脱氧-D-核糖调节的 HIF-1α 表达抑制可以防止缺氧诱导的线粒体上抗凋亡 Bcl-2 和 Bcl-X-L 的减少。 2-Deoxy-L-ribose及其类似物可以通过竞争性抑制2-deOXY-D-ribose的活性来增强细胞凋亡并抑制肿瘤的生长，因此这些类似物显示出抗肿瘤治疗的前景。 (C) 2002 年爱思唯尔科学（美国）。
An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-DeOXY-D-ribose, a degradation product of thymidine generated by TP enzymatic activity partially prevented hypoxia-induced apoptosis. 2-DeOXy-D-ribose inhibits a number of components of the caspase-mediated hypoxia-induced apoptotic pathway. It inhibits hypoxia-induced caspase 3 activation, mitochondrial cytochrome c release, downregulation of Bcl-2 and Bcl-x(L),, upregulation of hypoxia-inducible factor (HIF)-1alpha, and loss of mitochondrial transmembrane potential in human leukemia HL-60 cell line. These findings suggest a molecular mechanism by which 2-deOXY-D-ribose confers the resistance to apoptosis. Thus 2-deoxy-D-ribose-modulated suppression of HIF-1alpha expression could prevent the hypoxia-induced decrease of the anti-apoptotic Bcl-2 and Bcl-X-L on the mitochondria. 2-Deoxy-L-ribose and its analogs may enhance apoptosis and suppress the growth of tumors by competitively inhibiting the activities of 2-deOXY-D-ribose and thus these analogs show promise for anti-tumor therapy. (C) 2002 Elsevier Science (USA).